Tumor-associated transforming growth factor-beta and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients

In this study, we report coexpression of transforming growth factor-beta (T GF-beta) and interleukin-10 (IL-10) in pancreatic carcinoma tissue associat ed with significantly elevated levels of both cytokines in the sera of panc reatic carcinoma patients. Using conditioned media (Chl) of pancreatic carc inoma cells, we further demonstrate that tumor cell-derived TGF-beta and IL -10 inhibited in an additive fashion both proliferation and the development of Th1-like responses in peripheral blood mononuclear cell (PBMC) preparat ions derived from normal donors. The antiproliferative and Th1-suppressive activities contained in Chl of pancreatic carcinoma cells were due primaril y to IL-10 and/or TGF-beta, as shown by the capacity of cytokine-specific n eutralizing antibodies to reverse these effects. Finally, as compared to no rmal controls, PBMC derived from pancreatic carcinoma patients displayed a Th2-like cytokine expression pattern upon activation with either anti-CD3 a ntibody or Staphylococcus aureus strain Cowan I. Taken together, these resu lts suggest that aberrant production of TGF-beta and IL-10 in pancreatic tu mor patients skews T-cell cytokine production patterns in favor of a Th2 im munophenotype.